3-取代芳基氧化吲哚在肿瘤细胞内的定位  

Intracellular localization of 3-substituted aryl oxindole(PHⅡ-7)

作　　者：周园[1] 王彩云[1] 苏晔[1] 程昕[1] 彭洪薇[1] 杨纯正[1] 熊冬生[1] 

机构地区：[1]中国医学科学院北京协和医学院血液学研究所实验血液学国家重点实验室,天津300020

出　　处：《中国药理学通报》2009年第6期751-754,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30570772;30873091);天津市科技计划资助项目(No08ZCGHHZ00900)

摘　　要：目的观察3-取代芳基氧化吲哚(PHⅡ-7)在肿瘤细胞内的定位。方法通过化学合成的方法,在PHⅡ-7的1位引入氨烷基侧链,并将其氨基端进行FITC衍生化,在进行此衍生物体外抗肿瘤活性测定后,用激光共聚焦成像技术进行其在肿瘤细胞内的定位。结果成功合成具有氨烷基侧链的PHⅡ-7衍生物,并使之与FITC偶联;合成衍生物具有一定体外抗肿瘤活性;随着PHⅡ-7作用时间的增加,药物在肿瘤细胞系K562及其耐药肿瘤细胞系K562/A02中均逐渐由细胞质向细胞核内聚集。结论对于肿瘤细胞系K562及其耐药肿瘤细胞系K562/A02,PHⅡ-7作用靶位均为细胞核。Aim To study the intracellular location of 3-subsittuted aryl oxindole （ PHⅡ -7 ） in tumor cells. Methods The derivative with amino-alkyl side chain at I site of PHⅡ-7 was synthesized and linked with FITC by organic chemistry approaches, and its in vitro activity was evaluated using human leukemic cell line K562 cell and its MDR subline K562/A02 cell in order to identify the intracellular location of PH Ⅱ-7 with eonfocal microscope. Results The derivative with amino-alkyI side chain in PH Ⅱ-7 was synthesized and linked with FITC successfully. The derivative inhibited the proliferation of leukemic K562 and its MDR subline K562/A02 cells. The main distribution locations of PH Ⅱ-7 changed from cytoplasm to nuclear as time passed in both human leukemic K562 and its MDR subline K562/A02 cells when observed with confocal microscope. Conclusion The target sites in which PH Ⅱ-7 takes function are nuclear in both human leukemic K562 and its MDR subline K562/A02 cells.

关 键 词：氧化吲哚衍生物 多药耐药 细胞内定位 共聚焦激 光扫描显微镜 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]